Graft-versus-host disease (GVHD) is a potentially lethal clinical complication arising from the transfer of alloreactive T lymphocytes into immunocompromised patients. Specifically, one major component of GVHD includes the transfer of mature donor CD3+ T lymphocytes present in the transplanted product into the immunocompromised recipient. Once infused, donor T cells recognize host cellular antigens, resulting in an immunoreactive cascade often affecting the liver, gastrointestinal tract and skin (1,2).
Current methods to prevent and treat GVHD have included general immune suppression following transplant, reduced intensity conditioning, and depletion or inhibition of alloreactive donor T lymphocytes prior to transfusion (2, 3). The clinical effectiveness of these methods, however, is limited by a variety of side effects. For example, general immune suppression leads to an increased risk of reactivated virus infections and opportunistic infections, while reduced intensity conditioning regimens are associated with increased relapse rates (3). Currently, the most promising prophylactic treatment for GVHD is depletion or inhibition of donor T lymphocytes. This can be accomplished through a variety of methods including lymphoablative cytotoxic agents, specific T lymphocyte inhibitors, and T cell depletion by selecting for CD34+ hematopoietic stem and progenitor cells (HSPC or HSPCs). These methods have proven effective at lowering the rates of GVHD; however, they are also associated with slower reconstitution of the recipient immune system, increased risk for life-threatening infections and potentially limited graft-versus-leukemia effect (4, 5).